The ultimate goal of this K01 proposal is to provide the applicant with additional training in basic science and molecular biology to establish himself as an independent scientist. The project elucidates the molecular mechanisms and the function of PTH/PTHrP receptor regulation of Extracellular signal regulated (ERK) mitogen-activated protein (MAP) kinases. The role of non-receptor tyrosine kinases as well as the role of receptor phosphorylation in PTH activation of ERK1/2 MAP kinases in osteoblastic cell lines will be explored. Furthermore, the role of ERK1/2 MAP kinases in osteoblastic cell proliferation, differentiation and apoptosis will be investigated. Primary osteoblastic cell culture from wild type and genetically engineered mice as well as several other biochemical and pharmacological tools will be employed to achieve the goals of the study.